Related Experiment Videos
Cyclosporin suppresses transplant arteriosclerosis in the aorta-allografted, cholesterol-clamped rabbit. Suppression
H O Andersen1, G Madsen, B G Nordestgaard
1Department of Clinical Biochemistry, Rigshospitalet, Copenhagen O, Denmark.
Arteriosclerosis and Thrombosis : a Journal of Vascular Biology
|June 1, 1994
Summary
Cyclosporin significantly reduces transplant arteriosclerosis in rabbits by inhibiting myointimal proliferation and decreasing aortic permeability to low-density lipoprotein. This immunosuppressant offers a potential therapeutic benefit for heart transplant recipients.
Area of Science:
- Cardiovascular Research
- Transplantation Immunology
- Pharmacology
Background:
- Transplant arteriosclerosis is a major long-term complication following heart transplantation.
- The role of the immunosuppressant cyclosporin in transplant arteriosclerosis is controversial, with suggestions of both aggravation and retardation.
- Understanding cyclosporin's precise effect is crucial for managing heart transplant outcomes.
Purpose of the Study:
- To investigate the effect of human therapeutic levels of cyclosporin on experimental transplant arteriosclerosis.
- To determine if cyclosporin influences the development of arteriosclerosis in aortic transplants.
- To elucidate the mechanisms underlying cyclosporin's impact on transplant arteriosclerosis.
Main Methods:
- A rabbit model of aortic transplantation was utilized.
- Plasma cholesterol levels were maintained at 5-7 mmol/L in hyperlipidemic groups.
- Cyclosporin was administered at human therapeutic levels.
- Biochemical and histological assessments quantified transplant arteriosclerosis severity.
- Low-density lipoprotein permeability in transplanted aortas was measured.
Main Results:
- Cyclosporin markedly suppressed transplant arteriosclerosis severity.
- Cholesterol content in aortic transplants was reduced by 70% (10 days) and 80% (20 days) in cyclosporin-treated rabbits (P < .01).
- Myointimal proliferation was completely inhibited after 20 days of cholesterol feeding in cyclosporin-treated animals (P < .05).
- Cyclosporin reduced aortic permeability to low-density lipoprotein by 90% (P < .01) in non-cholesterol-fed rabbits.
Conclusions:
- Cyclosporin significantly decreases the severity of transplant arteriosclerosis.
- The protective effect of cyclosporin appears to be mediated, in part, by reducing aortic lipoprotein permeability.
- These findings suggest a beneficial role for cyclosporin in preventing transplant arteriosclerosis in heart transplant patients.